Calcitriol is widely used for treating osteoporosis which is a representative disease affecting the elderly, and calcifediol which is activated vitamin D3, is used for treating osteomalacia, etc. Calcitriol, which is generated by two respective hydroxylations of vitamin D3 in the liver and kidney, is a biogenic material, and can be simply administered orally. Also, it is known that calcitriol physiologically promotes the absorption of calcium and phosphorus in gastrointestinal organs and the kidney, and thus shows a high therapeutic effect on osteoporosis.
Also, calcitriol is used for treating rickets, osteomalacia, hypoparathyroidism, chronic renal failure, hemodialysis patient's renal osteodystrophy, and psoriasis, and its therapeutic effect on prostate cancer or myelogenous leukemia has been recently reported well.
As a method for preparing calcitriol or calcifediol, a preparation method by organic chemical synthesis and microorganism fermentation has been conventionally known. The organic chemical synthesis has a disadvantage in that it requires a highly complicated technology and an expensive reaction process because a hydroxyl group has to be selectively introduced into a 1- or 25-position of a carbon chain in consideration of stereospecificity and regiospecificity in a chemical structure. Then, in order to solve this disadvantage, a bioconversion production method by microorganism fermentation was developed. A bioconversion reaction by a microorganism has already proved to be stereospecific and regiospecific. Accordingly, for the production of an activated vitamin D3, a conventional organic synthesis method can be replaced by an economical method by bioconversion using a microorganism's hydroxylation function.
However, in a conventional bioconversion method by microorganism fermentation, several disadvantages as described below were found.
First, since the production method is carried out by microorganism culture, there is a possibility of contamination. Also, as a production scale is enlarged, the possibility is increased. Especially, as a culture period is prolonged, an exposure to contamination becomes serious. Since such contamination occurs after the administration of vitamin D3 in concurrence with a main propagation, a cost for a precursor is consumed during the contamination. Second, a bioconversion by fermentation may cause a large range of change in production yield. This is caused by a microorganism's specific culture sensitivity and thus is inevitable. For this reason, it is required to maintain the constancy of the inside of a culture room to some extent under a predetermined condition. Accordingly, third, the overall cost for the maintenance of production facilities is increased. Fourth, productivity of the method has already reached the maximum value, and is in a stagnant state without further improvement. Thus, it cannot be determined that the method has the highest competitive power. Fifth, due to difficulty in separation and purification of impurities, an excessive separation cost may be calculated. Since only a specific material has to be separated and purified from the entire culture solution, a large-scale separation/purification is required. Thus, the cost may be proportionally increased.
Accordingly, in order to solve these disadvantages, it is urgently required to develop a novel method for producing high-purity calcitriol or calcifediol with a high yield.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.